Charles E. Schmidt College of Medicine, Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL, USA.
Seattle Biomedical Research Institute, Seattle, WA, USA.
Sci Rep. 2018 Dec 14;8(1):17871. doi: 10.1038/s41598-018-36071-2.
Major complications and mortality from Plasmodium falciparum malaria are associated with cytoadhesion of parasite-infected erythrocytes (IE). The main parasite ligands for cytoadhesion are members of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. Interactions of different host receptor-ligand pairs may lead to various pathological outcomes, like placental or cerebral malaria. It has been shown previously that IE can bind integrin αVβ3. Using bead-immobilized PfEMP1 constructs, we have identified that the PFL2665c DBLδ1_D4 domain binds to αVβ3 and αVβ6. A parasite line expressing PFL2665c binds to surface-immobilized αVβ3 and αVβ6; both are RGD motif-binding integrins. Interactions can be inhibited by cyloRGDFV peptide, an antagonist of RGD-binding integrins. This is a first, to the best of our knowledge, implication of a specific PfEMP1 domain for binding to integrins. These host receptors have important physiological functions in endothelial and immune cells; therefore, these results will contribute to future studies and a better understanding, at the molecular level, of the physiological outcome of interactions between IE and integrin receptors on the surface of host cells.
疟原虫恶性疟疾的主要并发症和死亡率与寄生虫感染的红细胞（IE）的细胞黏附有关。细胞黏附的主要寄生虫配体是恶性疟原虫红细胞膜蛋白 1（PfEMP1）家族的成员。不同的宿主受体-配体对的相互作用可能导致各种病理结果，如胎盘或脑疟疾。先前已经表明，IE 可以结合整合素 αVβ3。我们使用珠固定的 PfEMP1 构建体，已经鉴定出 PFL2665c 的 DBLδ1_D4 结构域与 αVβ3 和 αVβ6 结合。表达 PFL2665c 的寄生虫系与表面固定的 αVβ3 和 αVβ6 结合；两者都是 RGD 基序结合的整合素。相互作用可以被 cyloRGDFV 肽抑制，这是 RGD 结合整合素的拮抗剂。这是首次，据我们所知，一个特定的 PfEMP1 结构域对整合素的结合的暗示。这些宿主受体在血管内皮细胞和免疫细胞中有重要的生理功能；因此，这些结果将有助于未来的研究，并更好地理解 IE 与宿主细胞表面整合素受体之间相互作用的生理结果。
